IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Role of p21 on the replication of damaged DNA.
Autor/es:
MANSILLA SF, SPERONI J, FEDERICO MB, VALLERGA MB, HABIF M, GOTTIFREDI V.
Lugar:
Montevideo
Reunión:
Workshop; XVII ALEXANDER HOLLAENDER COURSE, ?Environmental Genetics, Epigenetics and Genomic Instability?; 2012
Institución organizadora:
Alexander Hollaender courses
Resumen:
Mansilla Sabrina, Soria Gastón, Speroni Juliana, Federico M. Belen, Habif Martin, Vallerga M. Belen, Gottifredi Vanesa. Buenos Aires, Argentina. Our laboratory has found that the cyclin dependent kinase inhibitor p21 is degraded when cells are challenged with UV light. Different lines of evidences indicated that p21 degradation could result from the activation of DNA replication auxiliary mechanisms. In fact, since replicative polymerases cannot accommodate damage DNA. To avoid cell death, mechanisms such as translesion DNA synthesis, TLS, aid DNA replication and prevents irreversible stalling. During TLS, replicative polymerases are replaced by TLS polymerases that bypass DNA lesions. While many positive regulators of TLS were described, little is known about the mechanisms of negative regulation of TLS. We have found that PCNA (Proliferating Cell Nuclear Antigen) binding by p21 impairs the recruitment of many TLS polymerases to replication foci after UV irradiation. In line, forced p21 stabilization triggers excessive stalling of DNA replication and the accumulation of DNA damage markers such as gH2AX and 53BP1. Moreover, stable p21 expression after UV causes increased cell death. Together our data suggest that while basal p21 levels might prevent unnecessary loading of TLS polymerases at replication forks, p21 degradation after UV might promote cell survival by preventing replication stalling.